In the past several years we have accumulated evidence to implicate thiamine (a) in the conduction process in nervous tissue and (b) in the fatal, genetic disease, Subacute Necrotizing Encephalomyelopathy (Leigh's Disease). Our current plans are to determine the function of thiamine electrophysiologically by examining the effects of thiaminase on the giant axon of the squid and on the node of Ranvier of the frog. Biochemical studies include an investigation of the turnover of thiamine phosphate esters in vivo, the nature of the binding of thiamine in lobster and rat axolemmal membranes and the effect of thiamine antimetabolites on the binding of tetrodotoxin to sodium channels. In Leigh's Disease, we will attempt to purify and characterize the "inhibitor" found in the urine of patients.